Clinical and laboratory investigations will be done on arginase and in hyperargininemia due to an inherited deficiency of arginase in human subjects. Three patients known to be deficient in arginase will be studied during dietary and clinical trials to assess the impact of the enzyme deficiency on intracellular and extracellular amino acid and organic acid pools, the incorporation of (15N) ammonia into amino acids and urea and the therapeutic response to protein-free semi-synthetic diets supplemented only with essential amino acids or their keto-acid analogues. Normal human arginase will be purified to homogeneity from liver obtained at the time of death and will be administered to the patients in a study of enzyme replacement therapy. Arginase activity and properties in other human tissues will be studied and compared to the liver enzyme to define the number of gene loci specifying this enzyme in man. The activity and properties of arginase in red blood cells obtained from 16-20 week abortuses will be compared to that in newborns and older children in an attempt to show that they are specified by a single gene locus and thus establish the basis for prenatal diagnostic test. Long-term lymphocyte cell lines will be established from arginase-deficient and from control subjects and will be used as a laboratory model for the clinical enzyme deficiency state. The response of the cells to different growth media, including the distribution of labelled carbon into the urea cycle intermediates and urea and the activity of the urea cycle enzymes will be studied. These cells will also be used to study the effect of different concentrations of arginine on the active transport of other amino acids into the cell.